We examined longitudinal associations between the apolipoprotein E epsilon4 allele (ApoE4(+) status) and several cognitive outcomes and tested effect modification by sex in 644 non-Hispanic Caucasian adult participants from the Baltimore Longitudinal Study of Aging (BLSA). Dementia onset, cognitive impairment and decline were assessed longitudinally. After 27.5 years median follow-up, 113 participants developed dementia. ApoE4(+) predicted dementia significantly (hazard ratio HR = 2.89;95% confidence interval CI, 1.93-4.33), with nonsignificant sex differences. Taking all time points for predicting cognition, women had significantly stronger positive associations than men between ApoE4(+) status and impairment or decline on the California Verbal Learning Test (CVLT;delayed recall and List A total recall) and on Verbal Fluency Test-Categories. This ApoE4 x sex interaction remained significant with Bonferroni correction only for CVLT-delayed recall. Taking time points prior to dementia for cognitive predictions, the positive association between impairment in CVLT-delayed recall and ApoE4(+) status remained stronger among women, though only before Bonferroni correction. While ApoE4+ status appears to be a sex neutral risk factor for dementia, its association with verbal memory and learning decline and impairment was stronger among women. We examined the relations between the use of nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin and age-related change in multiple domains of cognitive function in community-dwelling individuals without dementia. The sample consisted of 2,300 participants from the Baltimore Longitudinal Study of Aging free of diagnosed dementia with measures obtained on one to 18 occasions over up to 45 years. At each visit, reported NSAID or aspirin use (yes/no) and tests of verbal and visual memory, attention, perceptuo-motor speed, confrontation naming, executive function, and mental status. RESULTS: Mixed-effects regression models revealed that NSAID use was associated with less prospective decline on the Blessed Information-Memory-Concentration (I-M-C) Test, a mental status test weighted for memory and concentration (P<.001), and Part B of the Trail Making Test, a test of perceptuo-motor speed and mental flexibility (P<.05). In contrast, aspirin use was related to greater prospective decline on the Blessed I-M-C Test (P<.05) and the Benton Visual Retention Test, a test of visual memory (P<.001). Consistent with studies of incident dementia, NSAID users without dementia displayed less prospective decline in cognitive function, but on only two cognitive measures. In contrast, aspirin use was associated with greater prospective cognitive decline on select measures, potentially reflecting its common use for vascular disease prophylaxis. Effect sizes were small, calling into question clinical significance, although overall public health significance may be meaningful. Though clinical cardiovascular and cerebrovascular diseases are established risk factors for cognitive decline and dementia, less is known about the relations between vascular health and cognition among individuals without these diseases. Carotid intimal medial thickness (IMT), a measure of subclinical vascular disease, is associated with concurrent decrements in cognitive function, but relatively little research has examined longitudinal relations between carotid IMT and prospective cognitive decline. We examined relations of carotid IMT to prospective trajectories of cognitive function among 538 (aged 20 to 93, 39% male, 66% white) participants in the Baltimore Longitudinal Study of Aging (BLSA) free of known cardiovascular, cerebrovascular, and neurological disease. Participants underwent initial carotid ultrasonography and repeat neuropsychological testing on up to 8 occasions over up to 11 years of follow-up. Mixed-effects regression analyses were adjusted for age, gender, race, education, mean arterial pressure, body mass index, total cholesterol, smoking, depressive symptoms, and cardiovascular medication use. Individuals with greater carotid IMT displayed accelerated decline in performance over time on multiple tests of verbal and nonverbal memory, as well as a test of semantic association fluency and executive function. These results suggest that carotid IMT predicts accelerated cognitive decline, particularly in the domain of memory, among community-dwelling individuals free of vascular and neurological disease. A history of depression has been linked to an increased dementia risk. This risk may be particularly high in recurrent depression due to repeated brain insult. We investigated whether there is a dose-dependent relationship between the number of episodes of elevated depressive symptoms (EDS) and the risk for mild cognitive impairment (MCI) and dementia. A total of 1,239 older adults from the Baltimore Longitudinal Study of Aging were followed for a median of 24.7 years. Diagnoses of MCI and dementia were made based on prospective data. Participants completed the Center for Epidemiologic Studies Depression Scale at 1- to 2-year intervals and were considered to have an EDS if their score was >or = 16. Kaplan-Meier survival curves, log-rank test for trend for survivor functions, and Cox proportional hazards models were conducted to examine the risk of MCI and dementia by number of EDS. We observed a monotonic increase in risk for all-cause dementia and Alzheimer disease as a function of the number of EDS. Each episode was associated with a 14% increase in risk for all-cause dementia. Having 1 EDS conferred an 87%-92% increase in dementia risk, while having 2 or more episodes nearly doubled the risk. Recurrence of EDS did not increase the risk of incident MCI. Our findings support the hypothesis that depression is a risk factor for dementia and suggest that recurrent depression is particularly pernicious. Preventing the recurrence of depression in older adults may prevent or delay the onset of dementia. Obesity indices (e.g., body mass index, waist-to-hip ratio) show differential relationships to other health outcomes, though their association to neurocognitive outcome is unclear. We examined whether central obesity would be more closely associated with cognitive function in 1,703 participants from the Baltimore Longitudinal Study of Aging. Longitudinal mixed-effects regression models showed multiple obesity indices were associated with poorer performance in a variety of cognitive domains, including global screening measures, memory, and verbal fluency tasks. Obesity was associated with better performance on tests of attention and visuospatial ability. An obesity index by age interaction emerged in multiple domains, including memory and attention/executive function. Obesity indices showed similar associations to cognitive function, and further work is needed to clarify the physiological mechanisms that link obesity to poor neurocognitive outcome. Several blood pressure indexes of autonomic dysregulation have been associated previously with stroke, silent cerebrovascular disease, and decreased cognitive function. We examined the relations among systolic blood pressure (SBP) and diastolic blood pressure (DBP) reactivity and cognitive function in a sample of stroke- and dementia-free older adults . After adjusting for age, education, and resting blood pressure, greater SBP reactivity was associated with poorer performance on Digits Forward and greater DBP reactivity was associated with poorer performance on Digits Forward and the Boston Naming Test. The results suggest that greater BP reactivity was associated with poorer performance on tests of attention, verbal memory, and confrontation naming.